Bottom Line:
In the mature CNS it is well accepted that cortical sensory processing results in a rise in regional cerebral blood flow (rCBF).In contrast at P30, MUA remains stable during repetitive stimulation and is associated with an increase in rCBF.Further we characterize in both age groups the responses in NVC to single sensory stimuli.

Affiliation: Institute of Physiology, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.

ABSTRACTNeurovascular coupling (NVC) in the adult central nervous system (CNS) is a mechanism that provides regions of the brain with more oxygen and glucose upon increased levels of neural activation. Hemodynamic changes that go along with neural activation evoke a blood oxygen level-dependent (BOLD) signal in functional magnetic resonance imaging (fMRI) that can be used to study brain activity non-invasively. A correct correlation of the BOLD signal to neural activity is pivotal to understand this signal in neuronal development, health and disease. However, the function of NVC during development is largely unknown. The rodent whisker-to-barrel cortex is an experimentally well established model to study neurovascular interdependences. Using extracellular multi-electrode recordings and laser-Doppler-flowmetry (LDF) we show in the murine barrel cortex of postnatal day 7 (P7) and P30 mice in vivo that NVC undergoes a physiological shift during the first month of life. In the mature CNS it is well accepted that cortical sensory processing results in a rise in regional cerebral blood flow (rCBF). We show in P7 animals that rCBF decreases during prolonged multi-whisker stimulation and goes along with multi unit activity (MUA) fatigue. In contrast at P30, MUA remains stable during repetitive stimulation and is associated with an increase in rCBF. Further we characterize in both age groups the responses in NVC to single sensory stimuli. We suggest that the observed shift in NVC is an important process in cortical development that may be of high relevance for the correct interpretation of brain activity e.g. in fMRI studies of the immature central nervous system (CNS).

pone-0080749-g003: Single multi-whisker stimulation.Single stimulation of multiple whiskers (stimulus is indicated by the dashed green line) resulted in a biphasic rCBF response at P7 with an initial rise in rCBF that was followed by a rCBF decline. The rCBF showed a trend to recover to baseline (representative rCBF trace of 100 averaged 0.1 Hz recordings in one P7 mouse and the corresponding LFP trace in magenta, A). At P30 (B) single-whisker stimulation evoked a small rise in rCBF (corresponding LFP trace is depicted in magenta). Simultaneous recordings of MUA revealed an initial maximum following stimulation (C, representative MUA PSTH plot of 100 recordings in one P7 mouse, inset exemplifies MUA peak delay upon stimulation) that was followed by a delayed MUA response in P7 lasting about 2 seconds. At P30 stimulation resulted in a similar MUA response but the delayed MU activity was not as strong as in P7 mice (representative MUA recording of one P30 mouse D). Single multi-whisker stimulation resulted in a similar amount of maximum MUA recruitment at both age groups (E). MU activity peak delay was significantly longer at P7 compared with P30 (F) whilst the maximum increase of rCBF was higher at P7 compared with P30 within the first 5 seconds after single stimulation (G). Grey shades in panels A and B indicate + SEM. Note that SEM does not visualize in LFP traces due to very small SEM.

pone-0080749-g003: Single multi-whisker stimulation.Single stimulation of multiple whiskers (stimulus is indicated by the dashed green line) resulted in a biphasic rCBF response at P7 with an initial rise in rCBF that was followed by a rCBF decline. The rCBF showed a trend to recover to baseline (representative rCBF trace of 100 averaged 0.1 Hz recordings in one P7 mouse and the corresponding LFP trace in magenta, A). At P30 (B) single-whisker stimulation evoked a small rise in rCBF (corresponding LFP trace is depicted in magenta). Simultaneous recordings of MUA revealed an initial maximum following stimulation (C, representative MUA PSTH plot of 100 recordings in one P7 mouse, inset exemplifies MUA peak delay upon stimulation) that was followed by a delayed MUA response in P7 lasting about 2 seconds. At P30 stimulation resulted in a similar MUA response but the delayed MU activity was not as strong as in P7 mice (representative MUA recording of one P30 mouse D). Single multi-whisker stimulation resulted in a similar amount of maximum MUA recruitment at both age groups (E). MU activity peak delay was significantly longer at P7 compared with P30 (F) whilst the maximum increase of rCBF was higher at P7 compared with P30 within the first 5 seconds after single stimulation (G). Grey shades in panels A and B indicate + SEM. Note that SEM does not visualize in LFP traces due to very small SEM.

Bottom Line:
In the mature CNS it is well accepted that cortical sensory processing results in a rise in regional cerebral blood flow (rCBF).In contrast at P30, MUA remains stable during repetitive stimulation and is associated with an increase in rCBF.Further we characterize in both age groups the responses in NVC to single sensory stimuli.

Affiliation:
Institute of Physiology, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.

ABSTRACTNeurovascular coupling (NVC) in the adult central nervous system (CNS) is a mechanism that provides regions of the brain with more oxygen and glucose upon increased levels of neural activation. Hemodynamic changes that go along with neural activation evoke a blood oxygen level-dependent (BOLD) signal in functional magnetic resonance imaging (fMRI) that can be used to study brain activity non-invasively. A correct correlation of the BOLD signal to neural activity is pivotal to understand this signal in neuronal development, health and disease. However, the function of NVC during development is largely unknown. The rodent whisker-to-barrel cortex is an experimentally well established model to study neurovascular interdependences. Using extracellular multi-electrode recordings and laser-Doppler-flowmetry (LDF) we show in the murine barrel cortex of postnatal day 7 (P7) and P30 mice in vivo that NVC undergoes a physiological shift during the first month of life. In the mature CNS it is well accepted that cortical sensory processing results in a rise in regional cerebral blood flow (rCBF). We show in P7 animals that rCBF decreases during prolonged multi-whisker stimulation and goes along with multi unit activity (MUA) fatigue. In contrast at P30, MUA remains stable during repetitive stimulation and is associated with an increase in rCBF. Further we characterize in both age groups the responses in NVC to single sensory stimuli. We suggest that the observed shift in NVC is an important process in cortical development that may be of high relevance for the correct interpretation of brain activity e.g. in fMRI studies of the immature central nervous system (CNS).